Zhang Fan, Lin Junyu, Feng Dechao, Liang Jiayu, Lu Yiping, Liu Zhihong, Wang Xianding
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
West China Clinical Medical College, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2022 Sep 30;10:922995. doi: 10.3389/fcell.2022.922995. eCollection 2022.
Cuprotosis is a new form of programmed cell death induced by copper. We explored the correlation of cuprotosis with clear cell renal cell carcinoma (ccRCC) and constructed a cuprotosis-related signature to predict the prognosis of patients with ccRCC. The clinical and transcriptomic data of ccRCC patients were downloaded from The Cancer Genome Atlas (TCGA), cBioPortal, and GEO databases, and cuprotosis-related gene sets were contained in the previous study. A cuprotosis-related signature was developed based on data from TCGA and verified by data from cBioPortal and GEO databases. The immune cell infiltrates and the corresponding signature risk scores were investigated. Two independent cohorts of clinical trials were analyzed to explore the correlation of the signature risk score with immune therapy response. A signature containing six cuprotosis-related genes was identified and can accurately predict the prognosis of ccRCC patients. Patients with downregulated copper-induced programmed death had a worse overall survival (hazard ratio: 1.90, 95% CI: 1.39-2.59, < 0.001). The higher signature risk score was significantly associated with male gender ( = 0.026), higher tumor stage ( < 0.001), and higher histological grade ( < 0.001). Furthermore, the signature risk score was positively correlated with the infiltration of B cells, CD8 T cells, NK cells, Tregs, and T cells, whereas it was negatively correlated with eosinophils, mast cells, and neutrophils. However, no correlation between cuprotosis and response to anti-PD-1 therapy was found. We established a cuprotosis signature, which can predict the prognosis of patients with ccRCC. Cuprotosis was significantly correlated with immune cell infiltrates in ccRCC.
铜死亡是一种由铜诱导的新型程序性细胞死亡形式。我们探讨了铜死亡与肾透明细胞癌（ccRCC）的相关性，并构建了一个与铜死亡相关的特征来预测ccRCC患者的预后。ccRCC患者的临床和转录组数据从癌症基因组图谱（TCGA）、cBioPortal和GEO数据库下载，先前的研究中包含了与铜死亡相关的基因集。基于TCGA的数据开发了一个与铜死亡相关的特征，并通过cBioPortal和GEO数据库的数据进行验证。研究了免疫细胞浸润情况及相应的特征风险评分。分析了两个独立的临床试验队列，以探讨特征风险评分与免疫治疗反应的相关性。鉴定出一个包含六个与铜死亡相关基因的特征，该特征可以准确预测ccRCC患者的预后。铜诱导的程序性死亡下调的患者总生存期较差（风险比：1.90，9５％置信区间：1.39 - 2.59，P<0.001）。较高的特征风险评分与男性性别显著相关（P = 0.026）、肿瘤分期较高（P<0.001）和组织学分级较高（P<0.001）。此外，特征风险评分与B细胞、CD8 T细胞、NK细胞、调节性T细胞和T细胞的浸润呈正相关，而与嗜酸性粒细胞、肥大细胞和中性粒细胞呈负相关。然而，未发现铜死亡与抗PD - 1治疗反应之间存在相关性。我们建立了一个铜死亡特征，可预测ccRCC患者的预后。铜死亡与ccRCC中的免疫细胞浸润显著相关。
